OBJECTIVE: The evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype.
METHODS: A complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis.
RESULTS: The analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively.
CONCLUSIONS: The findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.

Transcatheter aortic valve replacement by alternate access sites allows for treatment of patients with unfavorable anatomy for a transfemoral approach. To our knowledge, we present the first reported case of successful transcatheter aortic valve replacement via the transcarotid approach in a 65-year-old man with a symptomatic severe bicuspid aortic valve stenosis and virtually atretic coarctation of the thoracic aorta.

UNASSIGNED: To compare 1-year outcomes in patients at low surgical risk with bicuspid aortic valve stenosis (AS) following transcatheter aortic valve replacement (TAVR) and low-risk patients with tricuspid AS following surgical aortic valve replacement (SAVR).
UNASSIGNED: The pivotal randomized, prospective, multicenter TAVR trials compared TAVR vs SAVR in patients with tricuspid AS. No such trials exist for bicuspid AS.
UNASSIGNED: The Low Risk Bicuspid Study is a prospective, single-arm, TAVR trial that enrolled 150 patients from 25 sites in the United States. A screening committee confirmed bicuspid anatomy and valve classification based on computed tomography using the Sievers classification. Annular measurements guided valve sizing. These patients were propensity-matched to the SAVR patients in the randomized Evolut Low Risk Trial using 1:1 5-to-1-digit Greedy method, resulting in 144 matched pairs. For both trials, an independent clinical events committee adjudicated all serious adverse events, and the same independent core laboratory assessed all echocardiograms.
UNASSIGNED: The 1-year composite of death, disabling stroke, or aortic valve-related rehospitalization for bicuspid TAVR vs tricuspid SAVR was 6 (4.2%) vs 6 (4.2%) (P = .99). The effective orifice area (2.2 ± 0.7 cm2 vs 2.0 ± 0.6 cm2) was larger and the valve gradient was lower (8.7 ± 3.9 mm Hg vs 11.2 ± 4.7 mm Hg) in the TAVR group at 1 year (both P < .001). Moderate/severe aortic regurgitation was present in 1 TAVR and 2 SAVR patients (0.8% vs 1.6%; P > .99).
UNASSIGNED: In this select group of low-risk bicuspid patients, in the short-term follow-up, TAVR appears to have similar outcomes to those seen in comparable low-risk tricuspid patients undergoing SAVR.

Transcatheter aortic valve replacement has emerged as a safe and effective alternative to surgical aortic valve replacement for patients with severe symptomatic aortic stenosis across the spectrum of surgical risks based on a series of foundational randomized clinical trials. Of note, patients with bicuspid aortic valve (BAV) disease were excluded from all these pivotal randomized trials, leaving a significant knowledge gap because BAVs are commonly encountered in patients referred for aortic valve surgery or intervention. In this comprehensive review, we aim to provide heart teams with a detailed insight into how to approach patients with BAV disease, focusing on imaging and characterization of bicuspid valves, an overview of surgical approaches, and an understanding of the current data behind the role of transcatheter aortic valve replacement for patients with BAV disease.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients\' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

BACKGROUND: In 2019, the US Food and Drug Administration (FDA) approved transcatheter aortic valve replacement (TAVR) for low-risk patients with symptomatic severe tricuspid aortic stenosis. However, bicuspid aortic valve (BAV) patients were included only in single-arm registries of pivotal low-risk TAVR trials, resulting in limited data for this subgroup.
METHODS: The LRT (Low Risk TAVR) trial was an investigator-initiated, prospective, multicenter study and the first FDA-approved investigational device exemption trial to evaluate the feasibility of TAVR with balloon-expandable or self-expanding valves in low-risk patients with symptomatic severe BAV stenosis. This analysis reports 2-year follow-up, assessing the primary outcome of all-cause mortality and evaluating clinical outcomes.
RESULTS: From 2016 to 2019, a total of 72 low-risk patients diagnosed with symptomatic, severe BAV stenosis underwent TAVR across six centers. Six patients were lost to follow-up. At 2-year follow-up, mortality was 1.5% (1 of 66 patients). Among the remaining 65 patients, four experienced nondisabling strokes (6.2%), while 2 (3.1%) developed infective endocarditis. No new permanent pacemakers were required beyond the 30-day follow-up, and no patients, including those with endocarditis, needed aortic valve re-intervention. At the 2-year echocardiography follow-up (n = 65), 27.8% of BAV patients showed mild aortic regurgitation, with none exhibiting moderate or severe regurgitation. The mean aortic gradient was 12.1 ± 4.1 mmHg, and the mean valve area was 1.7 ± 0.5 cm².
CONCLUSIONS: The 2-year follow-up confirms commendable clinical outcomes of TAVR in patients with bicuspid aortic stenosis, establishing its evident safety.

BACKGROUND: The impact of various imaging modalities on discordance/concordance between indexed aortic valve area (iAVA) and catheterization-derived mean transaortic pressure gradient (mPGcath) is unclear in patients with bicuspid aortic valve (BAV). This study aimed to compare iAVA measurements obtained using four different methodologies in BAV and tricuspid aortic valve (TAV) patients, using mPGcath as a reference standard.
METHODS: We retrospectively reviewed patients who underwent comprehensive assessment of AS, including two-dimensional (2D) transthoracic echocardiography (TTE), three-dimensional (3D) transesophageal echocardiography (TEE), multidetector computed tomography (MDCT), and catheterization, at our institution between 2019 and 2022. iAVA was measured using the continuity eq. (CE) with left ventricular outflow tract area obtained by 2D TTE, 3D TEE, and MDCT, as well as planimetric 3D TEE.
CONCLUSIONS: Among 564 patients (64 with BAV and 500 with TAV), 64 propensity-matched pairs of patients with BAV and TAV were analyzed. iAVACE(2DTTE) led to overestimation of AS severity (BAV, 23.4%; TAV, 28.1%) and iAVACE(MDCT) led to underestimation of AS severity (BAV, 29.3%; TAV, 16.7%), whereas iAVACE(3DTEE) and iAVAPlani(3DTEE) resulted in a reduction in the discordance of AS grading. A moderate correlation was observed between mPGcath and iAVACE(3DTEE) (BAV, r = -0.63; TAV, r = -0.68), with iAVACE(3DTEE) corresponding to the current guidelines\' cutoff value (BAV, 0.58 cm2/m2; TAV, 0.60 cm2/m2). Discordance/concordance between iAVA and mPGcath in evaluating AS severity varies depending on the methodology and imaging modality used. The use of iAVACE(3DTEE) is valuable for reconciling the discordant AS grading in BAV patients as well as TAV.

BACKGROUND: Aortic wall shear stress (WSS) is a known predictor of ascending aortic growth in patients with a bicuspid aortic valve (BAV). The aim of this study was to study regional WSS and changes over time in BAV patients.
METHODS: BAV patients and age-matched healthy controls underwent 4D flow CMR. Regional, peak systolic ascending aortic WSS, aortic valve function, aortic stiffness measures and aortic dimensions were assessed. In BAV patients, 4D flow CMR was repeated after three years follow-up and both at baseline and follow-up computed tomography angiography (CTA) was acquired. Aortic growth (volume increase of ≥5%) was measured on CTA. Regional WSS differences within patients\' aorta and WSS changes over time were analysed using linear mixed-effect models and were associated with clinical parameters.
RESULTS: Thirty BAV patients (aged 34 years [IQR 25-41]) were included in the follow-up analysis. Additionally, another 16 BAV patients and 32 healthy controls (aged 33 years [IQR 28-48]) were included for other regional analyses. Magnitude, axial, and circumferential WSS increased over time (all p<0.001) irrespective of aortic growth. The percentage of regions exposed to a magnitude WSS >95th percentile of healthy controls increased from 21% (baseline 506/2400 regions) to 31% (follow-up 734/2400 regions) (p<0.001). WSS angle, a measure of helicity near the aortic wall, decreased during follow-up. Magnitude WSS changes over time were associated with systolic blood pressure, peak aortic valve velocity, aortic valve regurgitation fraction, aortic stiffness indexes, and normalized flow displacement (all p<0.05).
CONCLUSIONS: An increase of regional WSS over time was observed in BAV patients, irrespective of aortic growth. The increasing WSSs comprising a larger area of the aorta warrants further research to investigate the possible predictive value for aortic dissection.

Bicuspid Aortic Valves (BAV) are associated with an increased incidence of thoracic aortic aneurysms (TAA). TAA are a common aortic pathology characterized by enlargement of the aortic root and/or ascending aorta, and may become life threatening when left untreated. Typically occurring as the sole pathology in a patient, TAA are largely asymptomatic. However, in some instances, they are accompanied by aortic valve (AV) diseases: either congenital BAV or acquired in the form of Aortic Insufficiency (AI) or aortic stenosis (AS). When TAA are associated with aortic valve disease, determining an accurate and predictable prognosis becomes especially challenging. Patients with AV disease and concomitant TAA lack a widely accepted diagnostic approach, one that integrates our knowledge on aortic valve pathophysiology and encompasses multi-modality imaging approaches. This review summarizes the most recent scientific knowledge regarding the association between AV diseases (BAV, AI, AS) and ascending aortopathies (dilatation, aneurysm, and dissection). We aimed to pinpoint the gaps in monitoring practices and prediction of disease progression in TAA patients with concomitant AV disease. We propose that a morphological and functional analysis of the AV with multi-modality imaging should be included in aortic surveillance programs. This strategy would allow for improved risk stratification of these patients, and possibly new AV phenotypic-specific guidelines with more vigilant surveillance and earlier prophylactic surgery to improve patient outcomes.

UNASSIGNED: The ideal position of suture annuloplasty relative to the aortic annulus (internal or external) remains unclear. This study aimed to investigate the effectiveness of internal and external suture annuloplasty for isolated type 1 bicuspid aortic valve (BAV) repair. Electrocardiogram (ECG)-gated computed tomography (CT) was used to compare the two techniques and analyze their impact on the aortic annulus.
UNASSIGNED: We retrospectively analyzed 20 patients who underwent isolated type 1 BAV repair with either internal or external suture annuloplasty. Each group included 10 patients with comparable clinical features. Preoperative and postoperative ECG-gated CT scans were performed to assess the anatomical relationship between the ventricular-aortic junction (VAJ) and virtual basal ring (VBR), and to measure the height of annuloplasty from the VBR at predefined landmarks in both groups. Perioperative annular geometries, including annular area and perimeter, were measured to quantify the impact of annuloplasty on annular expansibility. The discrepancy between the postoperative annular dimension and size of the Hegar dilator were compared between groups to evaluate the effectiveness of annuloplasty.
UNASSIGNED: In both groups, VAJ was higher than VBR at the right coronary (RC) ostium (7.7 ± 3.3 mm) and the raphe (7.9 ± 1.5 mm). The height from the VBR to the external suture annuloplasty shared a similar pattern at the RC ostium and raphe (5.3 ± 1.1 mm and 4.8 ± 1.0 mm, respectively). In contrast, the height differences were minimal for these landmarks in the internal group. Postoperative annular area expansibility decreased in the internal group compared to preoperative levels (4.9 ± 2.3% vs. 8.9 ± 5.5%, p = 0.038), while no significant change was found in the external group (7.6 ± 4.1% vs. 6.5 ± 2.8%, p = 0.473). The internal group showed less area discrepancy between the VBR and the Hegar dilator both at systole (10.1 ± 3.7% vs. 30.1 ± 16.6%, p = 0.004) and diastole (5.7 ± 4.9% vs. 20.9 ± 14.5%, p = 0.009) compared to the external group.
UNASSIGNED: Internal suture annuloplasty results in better positioning relative to the VBR than external suture annuloplasty due to the absence of VAJ interference. While this results in more precise annular reduction and less expansibility in the short term, a long-term follow-up evaluation is necessary to assess its effectiveness.